1. Vitamin A: metabolism
Domina Petric, MD

2. Absorption of vitamin A
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

3. Absorption of retinoids
Most of the preformed vitamin A in the diet is in the form of retinyl esters.
Retinyl esters are hydrolyzed in the lumen of the small intestine to yield retinol.
This step is catalyzed by hydrolases produced by the pancreas and situated on the mucosal brush border or intrinsic to the brush border itself.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

4. Absorption of retinoids
The retinyl esters, as well as the carotenoids, are hydrophobic and, thus, depend on micellar solubilization for their dispersion in the aqueous environment of the small intestinal lumen.
Vitamin A is poorly utilized from low-fat diets!
The micellar solubilization of vitamin A facilitates access of soluble hydrolytic enzymes to their substrates.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

5. Absorption of retinoids
The overall absorption of retinol from retinyl esters appears to be fairly high (about 75%).
This process appears to be minimally affected by the level and type of dietary fat, although the absorption is appreciably less efficient at very high vitamin A doses .
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

6. Absorption of retinoids
Vitamin A can also be absorbed via non lymphatic pathways.
In mammals, the portal system may be an important alternative route of vitamin A absorption when the normal lymphatic pathway is blocked.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

7. Absorption of carotenoids
The major sources of vitamin A activity for most populations are the provitamin A carotenoids.
The carotenoids appear to be absorbed in the distal small intestine by micelle-dependent passive diffusion.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

8. Carotenoid metabolism linked to absorption
Some carotenoids can be provitamins A because they can be metabolized to yield retinal due to the action of retinal-forming carotene dioxygenases.
Most of this bioconversion occurs via the central cleavage of the polyene moiety by a predominantly cytosolic enzyme, β-carotene 15,15′-dioxygenase, found in the intestinal mucosa, liver and corpus luteum.
The enzyme requires iron as a cofactor.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

9. Retinoid metabolism linked to absorption
Retinal produced by at least the central cleavage step is reduced in the intestinal mucosa to retinol.
This step is catalyzed by another enzyme, retinaldehyde reductase, which is also found in the liver and eye.
The reduction requires a reduced pyridine nucleotide (NADH/NADPH) as a cofactor.
This step can be catalyzed by a short-chain alcohol dehydrogenase/aldehyde reductase.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

10. Mucosal metabolism of retinol
Retinol, formed either from the hydrolysis of dietary retinyl esters or from the reduction of retinal cleaved from β-carotene, is absorbed by facilitated diffusion via a specific transporter.
Then, retinol is quickly re-esterified with long- chain fatty acids in the intestinal mucosa.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11. Mucosal metabolism of retinol
Vitamin A is transported to the liver mainly (80 to 90% of a retinol dose) in the form of retinyl esters.
The composition of lymph retinyl esters is independent of the fatty acid composition of the most recent meal.
Retinyl palmitate typically comprises about half of the total esters.
Retinyl stearate comprises about a quarter.
Retinyl oleate and retinyl linoleate are present in small amounts.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

12. Two pathways for the enzymatic reesterification of retinol are:
A low-affinity route involves uncomplexed retinol.
It is catalyzed by acyl-CoA: retinol acyltransferase.
A high-affinity route involves retinol complexed with a specific binding protein, cellular retinol- binding protein type II.
It is catalyzed by lecithin–retinol acyltransferase.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

13. Vitamin A transport
II.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

14. Retinyl esters
Retinyl esters are secreted from the intestinal mucosal cells in the hydrophobic cores of chylomicron particles, by which absorbed vitamin A is transported to the liver through the lymphatic circulation, ultimately entering the plasma compartment through the thoracic duct.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

15. Transport of carotenoids
Carotenoids that are not metabolized at the intestinal mucosa are transported from that organ by chylomicra via the lymphatic circulation to the liver, where they are transferred to lipoproteins.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

16. Transport of carotenoids
The hydrocarbon carotenoids are transported primarily in low-density lipoproteins (LDLs).
The more polar carotenoids are transported in a more evenly distributed manner among LDLs and high-density lipoproteins (HDLs).
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

17. Transport of carotenoids
β-carotene is retained by the chylomicron remnants to be internalized by the liver for subsequent secretion in very low density lipoproteins (VLDLs).
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

18. Impact of abetalipoproteinemia
The absorption of vitamin A (as well as the other fat soluble vitamins) is a particular problem in patients with abetalipoproteinemia.
These patients lack apo B and can not synthesize any of the apo B-containing lipoproteins: LDLs, VLDLs, chylomicra.
Having no chylomicra, they show hypolipidemia and low plasma vitamin A levels.
When given oral vitamin A supplementation, their plasma levels are normal.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

19. Storage of vitamin A in the liver
Newly absorbed retinyl esters are taken up by the liver in association with chylomicron remnants by receptor-mediated endocytosis on the part of liver parenchymal cells.
Within those cells, remnants are degraded by lysosomal enzymes.
Retinol can be transferred from the parenchymal cells to stellate cells, where it is re-esterified.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

20. Retinyl ester hydrolysis
Vitamin A is mobilized as retinol from the liver by hydrolysis of hepatic retinyl esters.
This mobilization accounts for about 55% of the retinol discharged to the plasma (the balance comes from recycling from extrahepatic tissues).
The retinyl ester hydrolase involved in this process shows extreme variation between individuals.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

21. Retinol-binding protein
Once mobilized from liver stores, retinol is transported to peripheral tissues by means of a specific carrier protein, plasma retinol-binding protein (RBP).
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

22. Transport of retinoids
The transport, storage, and metabolism of the retinoids involve their binding to several other binding proteins, such as cellular retinol-binding protein types I and II, and cellular retinoic acid-binding protein types I and II.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

23. Cellular uptake of retinol
Due to their hydrophobic character, the plasma membranes do not present a barrier to retinol uptake.
Retinol can enter target cells by nonspecific partitioning into the plasma membrane from RBP, but most of the vitamin appears to enter cells through specific RBP (receptor-mediated mechanisms).
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

24. The majority of retinol that leaves the plasma appears to be recycled.
Retinol recycling
The majority of retinol that leaves the plasma appears to be recycled.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

25. Plasma retinol homeostasis
In healthy individuals, plasma retinol is maintained within a narrow range:
40–50 mg/ml in adults.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

26. Vitamin A in adipose tissue
Appreciable amounts of vitamin A are stored in adipocytes: 15–20% of total body store.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

27. Retinol is transferred from mother to infant through milk.
Milk retinol
Retinol is transferred from mother to infant through milk.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

28. Metabolism of vitamin A
III.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

29. Metabolism of vitamin A
The metabolism of vitamin A centers around the transport form, retinol, and the various routes of conversion available to it:
esterification
conjugation
oxidation
isomerization
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

30. Excretion of vitamin A IV.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

31. Excretion of vitamin A
Vitamin A is excreted in various forms in both the urine and feces.
Under normal physiological conditions, the efficiency of enteric absorption of vitamin A is high (80–95%), with 30–60% of the absorbed amount being deposited in esterified form in the liver.
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

32. Literature
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc
9/18/2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc